title: Cyclosporine alters correlation between free and total mycophenolic acid in kidney transplant recipients in the initial phase.
abstract: OBJECTIVE
  The factors affecting the pharmacokinetics of free mycophenolic acid (MPA) and its phenolic glucuronide (MPAG) are still unclear. The aim of this study was to evaluate the influence of cyclosporine on the pharmacokinetics of free MPA and MPAG.
  
  
  METHODS
  Seventy-seven kidney transplant recipients (23 were in an initial phase and 54 in a stable phase; 41 were treated with cyclosporine and 36 with tacrolimus) were enrolled. Free and total MPA and MPAG were determined using HPLC. The correlations between free and total predose concentrations (C(0) ) of MPA or MPAG were evaluated separately in patients receiving calcineurin inhibitor medications.
  
  
  CONCLUSIONS
  Serum concentration of albumin was lower in the initial phase than in the stable phase. A higher ratio of free MPAG C(0) to free MPA C(0) was observed in cyclosporine-treated than tacrolimus-treated kidney transplant recipients. Free MPA C(0) correlated weakly with total MPA C(0) in kidney transplant recipients treated with cyclosporine in the initial phase (ρ= 0·53, P = 0·06).
  
  
  CONCLUSIONS
  Cyclosporine increased the ratio of free MPAG C(0) to free MPA C(0) and varied the free fraction of MPA in the hypoalbuminaemic kidney transplant recipients in the initial phase.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Handayama, Higashi-ku, Hamamatsu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mino
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.forename: A
authors.initials: A
authors.lastname: Otsuka
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: S
authors.initials: S
authors.lastname: Ozono
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
authors.forename: J
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012709:Serum Albumin / Q000032:analysis; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D020719:Glucuronides; D007166:Immunosuppressive Agents; D012709:Serum Albumin; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus